PROJECT SUMMARY/ABSTRACT Clinical registries play a vital role in aggregating data to monitor diseases, measure and improve healthcare quality, and assess health outcomes. Despite the value of registries and laboratory data, laboratory results are typically (and inefficiently) abstracted manually from clinical sites to registries. Even when these data are electronically exchanged with registries, the process is often cumbersome and not standardized. Without adequate semantic interoperability, the burden of managing these variations limits the potential for registries to advance clinical practice, research, and policy-making. The U.S. Food and Drug Administration (FDA) recognizes the role of registries and the importance of interoperable laboratory data. The main goal of this cooperative agreement is to advance the semantic interoperability of laboratory test data exchange between health institutions and registries. Oncology will be the primary clinical domain for this work. To achieve FDA's objectives, RTI International, Intermountain Healthcare (IHC), and CancerLinQ (CLQ) (the RTI Team) have the following specific aims: AIM 1: Evaluate the technical requirements and readiness for electronic health record (EHR) to registry exchange of laboratory data using Fast Healthcare Interoperability Resources (FHIR). We will take a user- centered design approach to gather requirements and assess readiness. We will specify the structured metadata and controlled terminologies, specifically Logical Observation Identifiers Names and Codes (LOINC), needed in the data exchange. AIM 2: Develop and test the exchange of laboratory data from EHRs to a registry using FHIR. We will develop a FHIR Implementation Guide (IG) for EHR to registry exchange of laboratory data, which we will use to deploy software capabilities and conduct pilot tests of FHIR-based laboratory data exchange between IHC's commercial EHR and the CLQ registry. AIM 3: Test and evaluate the FHIR IG and system exchange of laboratory data from the EHR to registry using FHIR. We will further test and evaluate the FHIR IG and system exchange of laboratory data from the EHR to registries in an HL7 Connectathon. We will summarize test findings, recommendations, and the benefits of FHIR-based laboratory data exchange in a report to FDA. This project is significant because it addresses the central challenge of laboratory data interoperability by evaluating key national data standards for exchanging data between clinical systems and registries. The key innovation is to develop and evaluate the novel, standards-based exchange of laboratory data to registries using FHIR with pre-harmonized LOINC-coded tests. This project will advance the use of LOINC and FHIR in laboratory data exchange and inform current FDA and industry laboratory data initiatives, including the Systemic Harmonization and Interoperability Enhancement for Laboratory Data (SHIELD) collaborative.